Deep, Unbiased, and Quantitative Mass Spectrometry-Based Plasma Proteome Analysis of Individual Responses to mRNA COVID-19 Vaccine

Global campaign against COVID-19
have vaccinated a significant
portion of the world population in recent years. Combating the COVID-19
pandemic with mRNA vaccines played a pivotal role in the global immunization
effort. However, individual responses to a vaccine are diverse and
lead to varying vaccination efficacy. Despite significant progress,
a complete understanding of the molecular mechanisms driving the individual
immune response to the COVID-19 vaccine remains elusive. To address
this gap, we combined a novel nanoparticle-based proteomic workflow
with tandem mass tag (TMT) labeling, to quantitatively assess the
proteomic changes in a cohort of 12 volunteers following two doses
of the Pfizer-BioNTech mRNA COVID-19 vaccine. This optimized protocol
seamlessly integrates comprehensive proteome analysis with enhanced
throughput by leveraging the enrichment of low-abundant plasma proteins
by engineered nanoparticles. Our data demonstrate the ability of this
workflow to quantify over 3,000 proteins, providing the deepest view
into COVID-19 vaccine-related plasma proteome study. We identified
69 proteins with boosted responses post-second dose and 74 proteins
differentially regulated between individuals who contracted COVID-19
despite vaccination and those who did not. These findings offer valuable
insights into individual variability in response to vaccination, demonstrating
the potential of personalized medicine approaches in vaccine development.